JP3835815B2 - Enrofloxacin injection or infusion solution - Google Patents
Enrofloxacin injection or infusion solution Download PDFInfo
- Publication number
- JP3835815B2 JP3835815B2 JP52140496A JP52140496A JP3835815B2 JP 3835815 B2 JP3835815 B2 JP 3835815B2 JP 52140496 A JP52140496 A JP 52140496A JP 52140496 A JP52140496 A JP 52140496A JP 3835815 B2 JP3835815 B2 JP 3835815B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- solution
- weight
- enrofloxacin
- injection
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- SPFYMRJSYKOXGV-UHFFFAOYSA-N Baytril Chemical compound C1CN(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 SPFYMRJSYKOXGV-UHFFFAOYSA-N 0.000 title claims description 13
- 229960000740 enrofloxacin Drugs 0.000 title claims description 13
- 239000007924 injection Substances 0.000 title claims description 11
- 238000002347 injection Methods 0.000 title claims description 11
- 239000003978 infusion fluid Substances 0.000 title claims description 5
- 239000000243 solution Substances 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 238000001802 infusion Methods 0.000 claims description 5
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 4
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 claims description 4
- 235000012208 gluconic acid Nutrition 0.000 claims description 4
- 239000000174 gluconic acid Substances 0.000 claims description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 229940097043 glucuronic acid Drugs 0.000 claims description 3
- 239000004220 glutamic acid Substances 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- 239000011975 tartaric acid Substances 0.000 claims description 3
- 235000002906 tartaric acid Nutrition 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims 5
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 239000012895 dilution Substances 0.000 claims 1
- 238000010790 dilution Methods 0.000 claims 1
- 239000002253 acid Substances 0.000 description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 4
- 150000002596 lactones Chemical group 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 235000015165 citric acid Nutrition 0.000 description 3
- 239000004310 lactic acid Substances 0.000 description 3
- 235000014655 lactic acid Nutrition 0.000 description 3
- 235000011007 phosphoric acid Nutrition 0.000 description 3
- -1 quinolone carboxylic acids Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- PMNLUUOXGOOLSP-UHFFFAOYSA-N 2-mercaptopropanoic acid Chemical compound CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 229960003405 ciprofloxacin Drugs 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 description 1
- XOQQVKDBGLYPGH-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XOQQVKDBGLYPGH-UHFFFAOYSA-N 0.000 description 1
- ODJQKYXPKWQWNK-UHFFFAOYSA-N 3,3'-Thiobispropanoic acid Chemical compound OC(=O)CCSCCC(O)=O ODJQKYXPKWQWNK-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000004358 Butane-1, 3-diol Substances 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical class C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 239000003490 Thiodipropionic acid Substances 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 229960004393 lidocaine hydrochloride Drugs 0.000 description 1
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
- 239000004611 light stabiliser Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960001309 procaine hydrochloride Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 230000009993 protective function Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 235000019303 thiodipropionic acid Nutrition 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は、エンロフロキサシンの新規注射用もしくは注入用溶液に関する。
非経口投与用のキノロンカルボン酸の溶液が既に欧州特許第67 666号から知られている。これらは様々なヒドロキシカルボン酸との対応キノロンカルボン酸の塩に基づく。
過剰量の酸を伴う乳酸塩に基づく、キノロンカルボン酸、中でもシプロフロキサシンの注射用もしくは注入用溶液が欧州特許第138 018号により知られている。
酸が安定化のために添加されている約0.01〜0.5%のシプロフロキサシンの注入用水溶液が欧州特許第214 784号により知られている。前記文献では特に乳酸が好ましい酸として挙げられている。
微細なキノロンカルボン酸の懸濁物に基づく注入用溶液がドイツ特許出願公開第39 02 079号により知られている。
本発明は、以下の組成:
a)ポリヒドロキシカルボン酸もしくはアミノ酸またはそれらの混合物との塩の形態をとる、溶液の総重量に基づき0.1〜20重量%のエンロフロキサシン;
b)エンロフロキサシンに基づき0.1〜5モル過剰量のポリヒドロキシカルボン酸、アミノ酸、もしくはその混合物;
c)場合により、その溶液の総重量に基づき0.1〜30重量%の製剤補助剤;
d)100重量%になるまでの水:
の新規注射用および注入用溶液に関する。
これまでに知られるエンロフロキシンの注射用溶液と比較すると、本発明に従う溶液は迅速に生じる有力な効果という利点を有する。このことは活性物質の高血中レベルが投与後の短期間の内に達成されるという事実によってのみ示される。しかしながらその活性物質は更に迅速に排泄され、このことは特に食品生産に用いられる動物の治療においては大きな利点となる(短い待ち時間)。
本発明に従う注射用および注入用溶液は、好ましくは1〜10%、特に好ましくは2.5〜10%(溶液の総重量に基づく重量パーセント)の濃度の活性物質エンロフロキサシンを含む。
挙げることができるポリヒドロキシカルボン酸はグルコン酸、ガラクツロン酸、グルクロン酸、およびラクトビオン酸である。これらの酸は開鎖形態をとるかもしくはそれらのラクトンの形態をとることができる。これらの酸をラクトンとして用いる場合には、ラクトン環は、塩形成およびエンロフロキサシンとの複合体形成が生じる以前に少なくとも部分的には加水分解される。挙げることができるアミノ酸はグルタミン酸およびアスパラギン酸である。ポリヒドロキシカルボン酸もしくはアミノ酸は溶液のエンロフロキサシンの量に基づき0.1〜5モル過剰量で存在する。酸の過剰量は好ましくは0.2〜2モル、特に好ましくは0.5〜1モルである。
過剰量で存在する酸の部分は更に他の酸(例えば、塩酸、メタンスルホン酸、エタンスルホン酸、プロピオン酸、コハク酸、グルタール酸、クエン酸、アスコルビン酸、リン酸、もしくは乳酸)により置換され得る。
注射用の水に加え、注入用水溶液は更に、エタノール、グリセロール、プロピレングリコール、ポリエチレングリコール、およびトリエチレングリコールを、例えば液体賦形剤として含むことができる。pHは可能な限り、例えばリン酸、クエン酸、トリス(Tris)、アスコルビン酸、酢酸、コハク酸、酒石酸、グルコン酸、および乳酸、ならびにそれらの塩のような様々な物質を用いることにより3〜6.5の範囲の調節することができる。本発明に従う水性調製物のpHは3〜5.5、好ましくは3.5〜5である。水性懸濁物の重量オスモル濃度は200〜900mOsモル/kg、好ましくは260〜390mOsモル/kgであり、かつNaCl、グルコース、フルクトース、グリセロール、ソルビトール、マニトール、スクロース、もしくはキシリトール、またはそれらの物質の混合物の添加により等張条件にこの水性懸濁物を採用することができる。
例えば、増粘剤(一例では、中でもメチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ナトリウムカルボキシメチルセルロース、ポリビニルピロリドン、およびゼラチン)、吸収剤、軽質安定剤、結晶化遅延剤、錯化剤(一例では、中でもNaEDTA、リン酸、硝酸、酢酸、およびクエン酸)、酸化防止剤(中でも、アスコルビン酸、亜硫酸塩化合物、L−システイン、チオジプロピオン酸、チオ乳酸、モノチオグリセロール、およびプロピルガレート)、ならびに保存料(中でも、PHBエステル、フェノールおよび誘導体、クロロブタノール、ベンジルアルコール、エタノール、ブタノール、ブタン−1,3−ジオール、クロロヘキシジン塩、安息香酸および塩、ならびにソルビン酸)などの調製補助剤を更に用いることも可能である。例えば、塩酸プロカイン、および塩酸リドカインなどの局所麻酔剤を場合によっては本発明に従う溶液に添加することができる。
本発明に従う注射用もしくは注入用溶液を、対応する酸でのエンロフロキサシンからか、もしくはその水和物から出発させて調製することができる。
しかしながら塩形成に必要とされる量の酸を添加することによりその溶液中で直接塩を調製することも可能である。溶解は30℃と60℃との間の温度での作業により促進させることができる。この溶液は窒素ガス下で調製することができる。
この様式では、例えばアンプル、注射用バイアル、もしくは注入用ボトルのような適切な容器に充填された活性物質の即時使用用溶液か、または例えば濃縮物もしくは凍結乾燥物のような、そのような溶液の調製物に適する前駆体のいずれかを調製することが可能である。
その調製物が充填される容器は、ガラス製もしくはプラスチック製のいずれであってもよく、容器の材質がその容器に特別な保護機能(例えば、光もしくは酸素からの保護)を与える物質を含むことが可能である。
以下の実施例における溶液の調製を、伝熱ジャケットを付けたかもしくは付けていないバッチ容器内で実施することができる。非加熱用容器を用いる場合には、必要であらば予備加熱させた水を用いることができる。
一般的には溶媒の容積をその容器内に取り込ませ、そして個々の構成成分をそこで溶解させるが、溶媒を固体に添加することも可能である。
酸がそれらのラクトンの形態で用いられる場合には、それらは溶解後には、一般的にはその活性物質が添加される以前に加熱するかもしくは放置するかにより遊離酸へと加水分解される。そこで用いられる温度は40〜70℃、好ましくは50〜60℃である。
他の構成成分はその後には、撹拌させながら、冷却の後もしくは前にその調製物中に溶解させるかもしくは取り込ませる。残りの溶媒を補給した後には、その調製物を適切な細菌保持用フィルターを通して滅菌濾過し、および/または加熱滅菌することができる。
実施例
実施例1
実施例2
実施例3
実施例4
実施例5
実施例6
実施例7
The present invention relates to a novel injection or infusion solution of enrofloxacin.
A solution of quinolone carboxylic acid for parenteral administration is already known from EP 67 666. These are based on the salts of the corresponding quinolone carboxylic acids with various hydroxy carboxylic acids.
A solution for injection or infusion of quinolone carboxylic acids, in particular ciprofloxacin, based on lactate with an excess of acid is known from EP 138 018.
An injectable aqueous solution of about 0.01 to 0.5% ciprofloxacin with acid added for stabilization is known from EP 214 784. In said document, lactic acid is mentioned as a particularly preferred acid.
A solution for injection based on a suspension of fine quinolone carboxylic acids is known from DE 39 02 079.
The present invention has the following composition:
a) 0.1-20% by weight of enrofloxacin, based on the total weight of the solution, in the form of a salt with polyhydroxycarboxylic acid or amino acid or mixtures thereof;
b) 0.1-5 molar excess of polyhydroxycarboxylic acid, amino acid, or mixture thereof based on enrofloxacin;
c) optionally 0.1-30% by weight of formulation adjuvant, based on the total weight of the solution;
d) Water up to 100% by weight:
To new injectable and infusible solutions.
Compared to previously known solutions of enrofuroxin for injection, the solution according to the invention has the advantage of a powerful effect that occurs rapidly. This is only indicated by the fact that high blood levels of the active substance are achieved within a short period after administration. However, the active substance is excreted more rapidly, which is a great advantage (short waiting time), especially in the treatment of animals used for food production.
Injectable and infusion solutions according to the invention preferably contain the active substance enrofloxacin in a concentration of 1 to 10%, particularly preferably 2.5 to 10% (weight percent based on the total weight of the solution).
Polyhydroxycarboxylic acids that may be mentioned are gluconic acid, galacturonic acid, glucuronic acid and lactobionic acid. These acids can take the open chain form or the lactone form. When these acids are used as lactones, the lactone ring is at least partially hydrolyzed before salt formation and complex formation with enrofloxacin occurs. Amino acids that may be mentioned are glutamic acid and aspartic acid. The polyhydroxycarboxylic acid or amino acid is present in a 0.1-5 molar excess based on the amount of enrofloxacin in the solution. The excess amount of the acid is preferably 0.2 to 2 mol, particularly preferably 0.5 to 1 mol.
The acid part present in excess is further replaced by other acids (eg hydrochloric acid, methanesulfonic acid, ethanesulfonic acid, propionic acid, succinic acid, glutaric acid, citric acid, ascorbic acid, phosphoric acid or lactic acid). obtain.
In addition to water for injection, aqueous solutions for injection can further contain ethanol, glycerol, propylene glycol, polyethylene glycol, and triethylene glycol, for example, as liquid excipients. The pH is as much as possible by using various substances such as phosphoric acid, citric acid, Tris, ascorbic acid, acetic acid, succinic acid, tartaric acid, gluconic acid, and lactic acid, and salts thereof. A range of 6.5 can be adjusted. The pH of the aqueous preparation according to the invention is 3 to 5.5, preferably 3.5 to 5. The osmolality of the aqueous suspension is 200 to 900 mOsmol / kg, preferably 260 to 390 mOsmol / kg, and NaCl, glucose, fructose, glycerol, sorbitol, mannitol, sucrose, or xylitol, or the substance thereof. This aqueous suspension can be employed under isotonic conditions by the addition of a mixture.
For example, thickeners (in one example, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, and gelatin), absorbents, light stabilizers, crystallization retarders, complexing agents (in one example, among others) NaEDTA, phosphoric acid, nitric acid, acetic acid, and citric acid), antioxidants (among others, ascorbic acid, sulfite compounds, L-cysteine, thiodipropionic acid, thiolactic acid, monothioglycerol, and propyl gallate) and storage Preparation aids (among others, PHB esters, phenols and derivatives, chlorobutanol, benzyl alcohol, ethanol, butanol, butane-1,3-diol, chlorohexidine salts, benzoic acid and salts, and sorbic acid) It is also possible to further use. For example, local anesthetics such as procaine hydrochloride and lidocaine hydrochloride can optionally be added to the solution according to the invention.
Injectable or infusion solutions according to the invention can be prepared starting from enrofloxacin with the corresponding acid or starting from its hydrate.
However, it is also possible to prepare the salt directly in the solution by adding the amount of acid required for salt formation. Dissolution can be facilitated by working at temperatures between 30 ° C and 60 ° C. This solution can be prepared under nitrogen gas.
In this manner, a ready-to-use solution of the active substance in a suitable container such as an ampoule, injection vial or infusion bottle, or such a solution such as a concentrate or lyophilizate, for example. Any of the precursors suitable for this preparation can be prepared.
The container filled with the preparation may be made of glass or plastic, and the material of the container contains a substance that gives the container a special protective function (eg protection from light or oxygen). Is possible.
The preparation of solutions in the following examples can be carried out in batch vessels with or without a heat transfer jacket. When using a non-heating container, preheated water can be used if necessary.
Generally, the volume of solvent is taken into the vessel and the individual components are dissolved there, but it is also possible to add the solvent to the solid.
When acids are used in their lactone form, they are hydrolyzed to the free acid after dissolution, generally by heating or standing before the active agent is added. The temperature used there is 40-70 ° C, preferably 50-60 ° C.
The other components are then dissolved or incorporated into the preparation after stirring or before cooling with stirring. After replenishing the remaining solvent, the preparation can be sterile filtered and / or heat sterilized through a suitable bacteria retention filter.
Example
Example 1
Example 2
Example 3
Example 4
Example 5
Example 6
Example 7
Claims (2)
a)グルコン酸、グルクロン酸、グルタミン酸、酒石酸およびこれらの混合物からなる群より選ばれる有機酸との塩の形態にある、注射用または注入用溶液の総重量に基づき2.5〜10重量%のエンロフロキサシン;
b)エンロフロキサシンに基づき0.1〜5モル過剰量の前記有機酸;
c)場合により、上記溶液の総重量に基づき0.1〜30重量%の調製補助剤;および
d)100重量%になるまでの水。Injection or infusion solution having the following composition:
a) 2.5 to 10% by weight based on the total weight of the solution for injection or infusion in the form of a salt with an organic acid selected from the group consisting of gluconic acid, glucuronic acid, glutamic acid, tartaric acid and mixtures thereof Enrofloxacin;
b) 0.1-5 molar excess of the organic acid based on enrofloxacin;
c) optionally from 0.1 to 30% by weight of preparation aid based on the total weight of the solution; and d) water to 100% by weight.
b)エンロフロキサシンに基づき0.1〜5モル過剰量の前記有機酸;
c)場合により、注射用または注入用溶液の総重量に基づき0.1〜30重量%の調製補助剤;及び
d)100重量%になるまでの水:
の組成を有する注射用または注入用溶液の調製方法であって、エンロフロキサシンを前記有機酸の水溶液中で撹拌し、残りの調製補助剤を添加し、そして適切であるなら所望の濃度を水での稀釈により取得することを特徴とする方法。 a) 2.5 to 10% by weight based on the total weight of the solution for injection or infusion in the form of a salt with an organic acid selected from the group consisting of gluconic acid, glucuronic acid, glutamic acid, tartaric acid and mixtures thereof Enrofloxacin;
b) 0.1-5 molar excess of the organic acid based on enrofloxacin;
c) optionally 0.1 to 30% by weight of preparation aid, based on the total weight of the solution for injection or infusion; and d) water up to 100% by weight:
A method of preparing an injectable or infusible solution having the composition: wherein enrofloxacin is stirred in an aqueous solution of the organic acid, the remaining preparation adjuvants are added, and if desired, the desired concentration is adjusted. A method characterized in that it is obtained by dilution with water .
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19500784A DE19500784A1 (en) | 1995-01-13 | 1995-01-13 | Enrofloxacin solutions for injection or infusion |
DE19500784.0 | 1995-01-13 | ||
PCT/EP1995/005147 WO1996021453A1 (en) | 1995-01-13 | 1995-12-28 | Enrofloxacine injection or infusion solutions |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH10511967A JPH10511967A (en) | 1998-11-17 |
JP3835815B2 true JP3835815B2 (en) | 2006-10-18 |
Family
ID=7751383
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP52140496A Expired - Lifetime JP3835815B2 (en) | 1995-01-13 | 1995-12-28 | Enrofloxacin injection or infusion solution |
Country Status (28)
Country | Link |
---|---|
US (1) | US5998418A (en) |
EP (1) | EP0806955B1 (en) |
JP (1) | JP3835815B2 (en) |
CN (1) | CN1125635C (en) |
AR (1) | AR002265A1 (en) |
AT (1) | ATE261731T1 (en) |
AU (1) | AU695171B2 (en) |
BR (1) | BR9510444A (en) |
CA (1) | CA2210076C (en) |
CZ (1) | CZ293934B6 (en) |
DE (2) | DE19500784A1 (en) |
DK (1) | DK0806955T3 (en) |
ES (1) | ES2215183T3 (en) |
FI (1) | FI119970B (en) |
HU (1) | HU226826B1 (en) |
IL (1) | IL116726A (en) |
JO (1) | JO1883B1 (en) |
MX (1) | MX9705266A (en) |
NO (1) | NO313537B1 (en) |
NZ (1) | NZ298778A (en) |
PL (1) | PL182095B1 (en) |
PT (1) | PT806955E (en) |
RU (1) | RU2147225C1 (en) |
SK (1) | SK284348B6 (en) |
TW (1) | TW416852B (en) |
UA (1) | UA42819C2 (en) |
WO (1) | WO1996021453A1 (en) |
ZA (1) | ZA96244B (en) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6716830B2 (en) | 1998-09-30 | 2004-04-06 | Alcon, Inc. | Ophthalmic antibiotic compositions containing moxifloxacin |
DE102004054873A1 (en) * | 2004-11-12 | 2006-05-18 | Bayer Healthcare Ag | Treatment of mastitis |
DE102005055385A1 (en) * | 2004-12-09 | 2006-06-14 | Bayer Healthcare Ag | Medicines for hygienic application in the ear |
NZ555641A (en) * | 2004-12-09 | 2010-10-29 | Bayer Animal Health Gmbh | Stabilisation of glucocorticoid esters with acids |
CN100341510C (en) * | 2005-06-10 | 2007-10-10 | 冯莉萍 | 'Ennoxacin' micro-capsule, and its prepn. method |
FR2896416B1 (en) * | 2006-01-24 | 2010-08-13 | Vetoquinol | ANTI-INFECTIOUS COMPOSITION COMPRISING A PYRIDO (3,2,1-IJ) -BENZOXADIAZINE COMPOUND |
US7973022B2 (en) * | 2006-02-17 | 2011-07-05 | Idexx Laboratories, Inc. | Fluoroquinolone carboxylic acid salt compositions |
US20070197469A1 (en) * | 2006-02-17 | 2007-08-23 | Murthy Yerramilli V | Fluoroquinolone carboxylic acid salt compositions |
DE102006010642A1 (en) * | 2006-03-08 | 2007-09-27 | Bayer Healthcare Aktiengesellschaft | Drug formulations containing fluoroquinolones |
CN101230333B (en) * | 2007-01-26 | 2010-08-18 | 台湾尖端先进生技医药股份有限公司 | Single-strain antibody for enrofloxacin and detecting set thereof |
US20100247687A1 (en) * | 2009-03-30 | 2010-09-30 | Mary Arnold-Ronish | Formulation for tattoo removal and method of using same |
CN101810569B (en) * | 2010-05-22 | 2011-09-21 | 鼎正动物药业(天津)有限公司 | Enrofloxacin injection liquid and preparation method thereof |
CN103479569A (en) * | 2013-01-14 | 2014-01-01 | 四川喜亚动物药业有限公司 | Ciprofloxacin injection for animals and preparation method thereof |
RU2574007C2 (en) * | 2013-10-16 | 2016-01-27 | Олег Иванович Киселев | Injection solution for treating viral diseases specified in h1n1, h3n2, h5n1 influenza, tick-borne encephalitis and west nile fever |
US9993421B2 (en) * | 2015-11-20 | 2018-06-12 | Dynamo, Llc | Method for treating deleterious effects arising from tattoos |
CN107095848A (en) * | 2017-07-01 | 2017-08-29 | 山东中牧兽药有限公司 | A kind of enrofloxacin injection and preparation method thereof |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4670444B1 (en) * | 1980-09-03 | 1999-02-09 | Bayer Ag | and-naphthyridine-3-carboxylic acids and antibacte7-amino-1-cyclopropyl-4-oxo-1,4-dihydro-quinoline-rial agents containing these compounds |
HU188181B (en) * | 1981-06-11 | 1986-03-28 | Warner-Lambert Co,Us | Process for producing salts of naphtiridine and quinoline compounds of antimicrobial activity |
DE3537761A1 (en) * | 1985-10-24 | 1987-04-30 | Bayer Ag | INFUSION SOLUTIONS OF 1-CYCLOPROPYL-6-FLUOR-1,4-DIHYDRO-4-OXO-7- (1-PIPERAZINYL) -QUINOLINE-3-CARBONIC ACID |
-
1995
- 1995-01-13 DE DE19500784A patent/DE19500784A1/en not_active Withdrawn
- 1995-12-22 TW TW084113735A patent/TW416852B/en not_active IP Right Cessation
- 1995-12-27 AR ARP950100798A patent/AR002265A1/en unknown
- 1995-12-28 CA CA002210076A patent/CA2210076C/en not_active Expired - Lifetime
- 1995-12-28 AT AT95943218T patent/ATE261731T1/en active
- 1995-12-28 JP JP52140496A patent/JP3835815B2/en not_active Expired - Lifetime
- 1995-12-28 PL PL95321259A patent/PL182095B1/en not_active IP Right Cessation
- 1995-12-28 EP EP95943218A patent/EP0806955B1/en not_active Expired - Lifetime
- 1995-12-28 MX MX9705266A patent/MX9705266A/en unknown
- 1995-12-28 PT PT95943218T patent/PT806955E/en unknown
- 1995-12-28 BR BR9510444A patent/BR9510444A/en not_active IP Right Cessation
- 1995-12-28 AU AU44349/96A patent/AU695171B2/en not_active Expired
- 1995-12-28 DK DK95943218T patent/DK0806955T3/en active
- 1995-12-28 NZ NZ298778A patent/NZ298778A/en not_active IP Right Cessation
- 1995-12-28 WO PCT/EP1995/005147 patent/WO1996021453A1/en active IP Right Grant
- 1995-12-28 CZ CZ19972130A patent/CZ293934B6/en not_active IP Right Cessation
- 1995-12-28 US US08/875,061 patent/US5998418A/en not_active Expired - Lifetime
- 1995-12-28 UA UA97084225A patent/UA42819C2/en unknown
- 1995-12-28 CN CN95197749A patent/CN1125635C/en not_active Expired - Lifetime
- 1995-12-28 HU HU9800183A patent/HU226826B1/en not_active IP Right Cessation
- 1995-12-28 SK SK946-97A patent/SK284348B6/en not_active IP Right Cessation
- 1995-12-28 ES ES95943218T patent/ES2215183T3/en not_active Expired - Lifetime
- 1995-12-28 RU RU97113465A patent/RU2147225C1/en active
- 1995-12-28 DE DE59510878T patent/DE59510878D1/en not_active Expired - Lifetime
-
1996
- 1996-01-10 IL IL11672696A patent/IL116726A/en not_active IP Right Cessation
- 1996-01-11 JO JO19961883A patent/JO1883B1/en active
- 1996-01-12 ZA ZA96244A patent/ZA96244B/en unknown
-
1997
- 1997-07-10 NO NO19973223A patent/NO313537B1/en not_active IP Right Cessation
- 1997-07-11 FI FI972966A patent/FI119970B/en not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP3835815B2 (en) | Enrofloxacin injection or infusion solution | |
KR870003786A (en) | Leaching solution of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) -quinoline-3-carboxylic acid | |
JPS6094910A (en) | Lactate solution of piperazinyl-quinolone and piperazinyl-azaquinolone carboxylic acid | |
DK157731B (en) | STABLE PHARMACEUTICAL PREPARATIONS CONTAINING OXICAM DERIVATIVES AND PROCEDURES FOR PREPARING THEM | |
US5478829A (en) | Solution of sparfloxacin, its preparation and salt of which it is composed | |
JP2919112B2 (en) | Cephalosporin injection and production method thereof | |
KR100446098B1 (en) | Enlofloxacin injection or injection | |
JP2001519390A (en) | Pharmaceutical preparations containing glycine as stabilizer | |
JP2022500350A (en) | Method for Producing Stable Azacitidine-Containing Pharmaceutical Composition | |
AU2010259102B2 (en) | Ipamorelin diacetate injection and infusion solutions | |
KR101461271B1 (en) | Formulations for injection containing sivelestat sodium salt or hydrate thereof | |
JP4374250B2 (en) | Famotidine injection | |
JP3776334B2 (en) | Inulin-containing preparation | |
KR0159540B1 (en) | The salt of quinolone carboxylic acid and their pharmaceutical composition containing them | |
FI82378B (en) | FOERFARANDE FOER FRAMSTAELLNING AV INJISERBARA OXITETRACYKLINLOESNINGAR. | |
JPH11255653A (en) | Cephalosporin injection and its production | |
JP2002542288A (en) | Novel injectable anticoagulant composition | |
HU176305B (en) | Process for producing stabil tetracyclic compositions |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20040720 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20040708 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20041019 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20050712 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20051110 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20051201 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20060606 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060615 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20060711 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20060725 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090804 Year of fee payment: 3 |
|
R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090804 Year of fee payment: 3 |
|
R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
R371 | Transfer withdrawn |
Free format text: JAPANESE INTERMEDIATE CODE: R371 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090804 Year of fee payment: 3 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090804 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090804 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100804 Year of fee payment: 4 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110804 Year of fee payment: 5 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110804 Year of fee payment: 5 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120804 Year of fee payment: 6 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130804 Year of fee payment: 7 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130804 Year of fee payment: 7 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130804 Year of fee payment: 7 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
EXPY | Cancellation because of completion of term |